One major drawback of most cancer therapeutics is the lack of specificity and associated toxicity to normal tissues. A significant advance in therapeutic effectiveness would be likely achieved if cytotoxic agents could be delivered specifically to tumor cells, with minimal delivery to normal tissue. Conjugation of cytotoxic agents to molecules that bind specifically to a tumor target found would then enable tumor-specific delivery and would reduce non-specific toxicity.
Molecules that are found specifically on the surface of cancer cells are especially promising targets for tumor-specific homing molecules. An example of such a cell surface molecule is ErbB2 (also known as HER2 or neu). ErbB2 is a member of the ErbB family of growth factor receptors, which includes ErbB1 (also known as epidermal growth factor receptor). ErbB2 is a membrane protein containing a cysteine-rich extracellular domain (ECD), a transmembrane domain, and an intracellular tyrosine kinase domain. It is overexpressed on the surface of breast cancer cells in approximately 30% of newly diagnosed patients and is associated with a poor prognosis. Importantly, metastatic tumor cells in the bone marrow of 60–70% of breast cancer patients overexpress ErbB2 on their surface (Pantel et al., J Natl Cancer Inst 85:1419; Braun et al., Cancer Research, 61:1890). Therefore, ErbB2 is an extremely promising target molecule for some forms of cancer.